Inherited Metabolic Disorders
Inherited metabolic disorders are caused by genetic mutation, creating an enzyme deficiency that leads to an inability to breakdown metabolic waste products. The result is a progressive cellular accumulation of toxic substances, which damages organs, tissues, and the central nervous system.
If left untreated, these disorders result in a progressive disease with neurological and psychomotor retardation, skeletal abnormalities, and life-threatening cardiac and pulmonary complications. [1,2] Allogeneic hematopoietic cell transplantation (HCT) can arrest this progressive deterioration by introducing enzyme-producing cells that can cross the blood-brain barrier. [3]
A study of HCT in 217 patients with Hurler syndrome found that preservation of cognitive function at the time of transplant and a younger age at transplantation were major predictors for superior post-transplant cognitive development. [4]
Allogeneic HCT can treat:
- Hurler syndrome (MPS I)
- Hunter syndrome (MPS II) [5]
- Maroteaux-Lamy syndrome (MPS VI)
- Sly syndrome (MPS VII)
- Cerebral X-linked adrenoleukodystrophy
- Globoid-cell leukodystrophy (Krabbe disease)
- Metachromatic leukodystrophy
- Gaucher disease
- Fucosidosis
- Alpha-mannosidosis
- Aspartylglycosaminuria
- Mucolipidosis II (I-cell disease)
- Wolman syndrome
Outcomes
Review outcomes of allogeneic transplantation in patients with inherited metabolic disorders below. View additional slides showing demographic data and transplant trends.
Data in this section have been prepared by CIBMTR® (Center for International Blood and Marrow Transplant Research), our research program.
Figure 1: Pediatric Hurler Syndrome Survival, Unrelated Marrow HCT
Download slide "Pediatric Hurler Syndrome Survival, Unrelated Marrow HCT"
Figure 2: Pediatric ALD, MLD Survival, Unrelated Marrow HCT
Download slide "Pediatric ALD, MLD Survival, Unrelated Marrow HCT"
Referral Timing Guidelines
These guidelines highlight disease categories that include patients at risk for disease progression and who should be referred for a consultation for transplantation. [6]
Transplant Consultation Guidelines: Inherited Metabolic Disorders
(including Hurler syndrome, adrenoleukodystrophy, and others)- At diagnosis or if detected on newborn screening
View complete Referral Timing Guidelines
References
- Domen J, Gandy K, Dalal J. Emerging uses for pediatric hematopoietic stem cells. Pediatr Res. 2012; 71(4-2): 411-417. Access
- Boelens JJ, Orchard PJ, Wynn RF. Transplantation in inborn errors of metabolism: current considerations and future perspectives. Brit J Haematol. 2014; 167(3): 293-303. Access
- Prasad VK, Kurtzberg J. Transplant outcomes in mucopolysaccharidoses. Sem Hematol. 2010; 47(1): 59-69. Access
- Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015; 125(13): 2164-2172. Access
- Kubaski F, Yabe H, Suzuki Y, et al. Hematopoietic stem cell transplantation for patients with mucopolysaccharidosis II. Biol Blood Marrow Transplant. 2017; 23(10): 1795-1803. Access
- NMDP/Be The Match and ASBMT Recommended Timing for Transplant Consultation, 2018. Download (PDF)